The properties required of an X-ray contrast medium in order to visualize liver and spleen are recited in a publication by Thomas, S. F. and associates (Hepatolienography: Past, Present and Future. Radiology 57: 669-684, 1951). According to Thomas and associates such a contrast medium
1. shall have only slight acute or chronic toxicity or none at all; PA1 2. shall not be radioactive; PA1 3. shall contain elements of sufficiently high atomic number to provide a satisfactory X-ray density even when administered in moderate quantities; PA1 4. shall be capable of being administered intravenously without difficulty; PA1 5. shall have a high affinity for selective uptake in the liver and the spleen; and PA1 6. shall secrete quickly and positively from the body.
It is evident from the works discussed in the aforegoing that several of these requirements have already been satisfied. The most serious problem still to be resoloved is that of producing an emulsion of X-ray contrast agent which has small particle sizes and with properties which will enable the major part of the high-affinity emulsion particles to be taken-up selectively and evenly in the liver and the spleen.
The possibility of preparing emulsions which contain fat-soluble pharmaceuticals which are specifically taken-up by different body organs has attracted great interest since such emulsions were first prepared for intravenous injection about 20 years ago. In a summary, 1987, in the book "Biological Approaches to the Controlled Delivery of Drugs", (Annals of the New York Academy of Sciences, Vol. 507, Dec. 22, 1987: Lipid Emulsions as Drug Delivery Systems; S. S. Davies, et al, pages 75-88), there is discussed the possibility of directing the particles in fat emulsions to specific organs. Despite the fact that several possibilities of steering or directing the emulsion particles to different organs have been investigated, it is obvious that no important scientific or commercial advance has been made in this direction up to the present time.
The investigations carried out hitherto have shown that an emulsion which contains large particles is taken-up in the RES-cells of the liver and that, on the other hand, an emulsion which contains small particles is taken-up in the space of Disse and in the hepatocytes. It has been discovered that about 80% of the iodine-containing fat injected is taken-up by the liver when using an emulsion having a particle size of 1-3 .mu.m. On the other hand, only about 1/4-1/3 of the organically bound iodine is taken-up by the liver from an emulsion, which has a particle size of 0.1-0.3 .mu.m. It has become desirable to produce a stable iodine-containing emulsion with small particles that is taken-up by the liver to the same high extent as an iodine-containing emulsion with large particles. Hitherto, it has been considered impossible to produce an emulsion with such properties. In endeavours to control the liver uptake of an emulsion of iodized fat of small particle size, we have tested a large number different emulsion additives. Quite surprisingly, we discovered that this control could be achieved with certain additives, despite the particle size of the emulsion being so low as to render negligible any expectation of the emulsion being taken-up into the RES-system of the liver. Thus, as a result of the present invention, we have successfully prepared an iodine-containing fat emulsion which is stable, which can be autoclaved and which fulfils the requirements stated by Thomas and associates in a far better way than do earlier known iodine-containing fat emulsions.